A common misconception is that Wylde wrote the song as a tribute to his close friend "Dimebag" Darrell Abbott (former guitarist for bands Pantera and Damageplan), who was killed on December 8, 2004. In fact, he wrote the song many months prior to the incident, and subsequently began dedicating the song to him. On the topic of dedication, Wylde explains that he "was looking at the lyrics, and I just said 'Man, this has gotta be Dime's tune', so we just made it Dime's song and that's how the video came about. I think it's really emotional and it came out great. Everyone loves it – Vinnie Paul Abbott (Darrell's brother), Rita (Darrell's girlfriend). It's all about Dime's memory and there ain't a dry eye in the house every time you see it." Wylde also states that every time he plays a show, "it will never leave the Black Label set." During the "Pedal to the Metal" concert series, however, the song was not included in the set.
The music video for "In This River" features the childhood personage of Wylde and Abbott riding bicycles together and diving into a river. At the end of the video, only the adult version of Wylde emerges, symbolizing Darrell's death. Wylde explains that "The river is a metaphor for life in general, all the bullshit that you deal with from being a kid growing up. The whole thing's just about life and death."